Editor Associate Editor for Gynecology

Editor

Associate Editor for Gynecology

Dev Maulik

Ivica Zalud

Doppler Ultrasound

in Obstetrics and Gynecology

Doppler Ultrasound

in Obstetrics and Gynecology

2nd Revised and Enlarged Edition

Editor

Associate Editor for Gynecology

Dev Maulik

Ivica Zalud

With 521 Figures and 112 Tables

1 2

Editor

Dev Maulik, MD, Ph.D.

Winthrop University Hospital

Department of Obstetrics and Gynecology, 159 First Street

Mineola, NY 11501 USA

Associate Editor for Gynecology Ivica Zalud, MD, Ph.D.

Kapiolani Medical Center for Women and Children 1319 Punahou Street

Honolulu, HI 96826 USA

ISBN 0-387-94240-8 Springer-Verlag New York Berlin Heidelberg, First edition

Library of Congress Control Number: 2005923619

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Editor: Dr. Ute Heilmann, Springer-Verlag, Heidelberg Desk editor: Wilma McHugh, Springer-Verlag, Heidelberg Production: ProEdit GmbH, Elke Beul-Gæhringer, Heidelberg Cover design: Estudio Calamar, F. Steinen-Broo, Pau/Girona, Spain Typesetting: K+V Fotosatz GmbH, Beerfelden

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ISBN-10 3-540-23088-2 Springer-Verlag Berlin Heidelberg New York

ISBN-13 978-3-540-23088-5 Springer-Verlag Berlin Heidelberg New York

To the loving memory of my mother

Tara Devi

(1910±1994)

It is with great pleasure we offer the second edition of ªDoppler Ultrasound in Obstetrics and Gynecol- ogyº to our readers. We remain deeply appreciative of the success of the first edition with its continuing enthusiastic reception from our readers.

Impressive advances have occurred in diagnostic Doppler sonography since the publication of the first edition of the book. With the ever-increasing emphasis on evidence-based medicine, the clinical applications of fetal Doppler ultrasound have become progressively more refined, although significant uncertainty still con- tinues in many areas, providing opportunities for fu- ture investigations. Ultrasound technology and instru- mentation have become increasingly more sophisti- cated and user friendly. Exciting technological innova- tions and breakthroughs, such as the emergence of real- time three-dimensional sonography, are offering huge potentials for Doppler assessment of the cardiovascular system. These advances have provided a powerful ratio- nale for bringing the book up to date so that it may con- tinue to serve our readers in the future. In this process, we have comprehensively and critically examined the information contained in the first edition, and revised and expanded it as deemed appropriate.

The second edition now boasts 40 chapters, ex- panded from 34 chapters in the previous edition. This results from the inclusion of eight new chapters and condensation of three gynecology chapters into one.

In addition, there have been substantial revisions of the other preexisting chapters. To give the readers an overall sense of the contents, these changes are summa- rized here. The introductory chapters continue to deal with the basic principles of Doppler sonography, he- modynamics, fetal and maternal cardiovascular phys- iology, and biosafety and have been extensively revised.

We have added two new chapters, one reviewing the ve- nous hemodynamics and the other dealing with three- dimensional color and power Doppler ultrasound. The subsequent chapters have been significantly strength- ened by the addition of with six new chapters dealing with the following topics: intrauterine blood flow; post- natal neurological development; clinical application of cerebral Doppler sonography; Doppler ultrasound ex- aminations of the fetal coronary circulation, the umbi- lical venous flow, and the fetal pulmonary venous cir-

culation; four-dimensional B-mode and color Doppler fetal echocardiography; and three-dimensional Dop- pler sonography in gynecology. The three previous separate chapters on Doppler ultrasound for benign gynecological disorders, ectopic pregnancy, and infer- tility have been combined into one single more cohe- sive and concise chapter. After implementation of these additions and revisions, the book now has 521 illustra- tions and 112 tables. Moreover, all the illustrations in- cluding the color plates are now incorporated in the text, which should significantly improve the ease of perusal for our readers.

In this complex and extensive endeavor, we have been greatly assisted by internationally recognized ex- perts in the field who have generously and enthusiasti- cally participated in this venture despite their enor- mous responsibilities and hectic schedules. I am truly obliged to my colleagues who were instrumental in making the first edition a success and who have up- dated their chapters for the second edition to reflect the changes that have developed in their areas of exper- tise. I am particularly indebted to those authors who, in addition to updating their chapters from the first edi- tion, have kindly contributed new chapters. I take this opportunity to welcome the 23 new authors who have substantially contributed to enriching this edition. As well as those authors who have added new chapters to the book, several of the new authors have rewritten and updated chapters from the first edition. I am truly grateful to Dr. Ivica Zalud for his professional and edi- torial assistance in reorganizing and updating the chapters on gynecological Doppler ultrasound. I re- main forever indebted to all my distinguished collea- gues not only for their support in making this second edition a reality but also for their scholarly activities that continue to energize the progress in this field.

Finally, all our efforts will be worthwhile if our readers find this new edition of the book useful and stimulating for their education and clinical practice.

It would be especially gratifying if the contents in- spire and assist new investigations that make further progress in the development of Doppler sonography with the aim of improving women's health.

Summer 2005 Dev Maulik

Preface

I would like to express my gratitude to Springer-Ver- lag GmbH & Co., Heidelberg, for the publication of this book, and in particular Dr. Ute Heilmann, Execu- tive Editor Clinical Medicine at Springer-Verlag, for her enthusiastic support and for facilitating the com- pletion of this second edition and Wilma McHugh, Medical Desk Editor, for her help in production work.

I would also like to express my sincere thanks to Wendie Irving, my editorial assistant at Winthrop-

University Hospital, for her invaluable assistance and tireless dedication in the preparation of this book.

Finally, most of my activities related to this pro- ject occurred in the evenings and the weekends at home. I am deeply appreciative and thankful to my wife Shibani and our children, Devika and Davesh, for their encouragement and support during this long process.

Acknowledgements

1 Doppler Sonography: A Brief History . . 1

Dev Maulik Christian Andreas Doppler and the Doppler Theory . . . . 1

Verification of Doppler's Theory . . . . 3

Technical Utilization of Doppler's Principle 4 Development of Spectral Doppler Ultra- sonography . . . . 4

Development of Color Doppler Ultrasonography . . . . 5

Introduction of Doppler Ultrasonography to Obstetrics and Gynecology . . . . 5

Conclusion . . . . 6

References . . . . 6

2 Physical Principles of Doppler Ultrasonography . . . . 9

Dev Maulik Propagation of Sound . . . . 9

Propagation Speed of Sound . . . . 10

Wavelength, Frequency, Pulse . . . . 10

Amplitude, Power, Intensity . . . . 11

Ultrasound and Piezoelectric Effect . . . . . 11

Characteristics of Sound Transmission in a Medium . . . . 12

Doppler Effect . . . . 13

Doppler Ultrasound . . . . 13

Backscattering . . . . 14

Magnitude of Doppler Shift . . . . 15

Angle Dependence of Doppler Shift . . . . 16

References . . . . 17

3 Spectral Doppler: Basic Principles and Instrumentation . . 19

Dev Maulik Doppler Signal Processing . . . . 19

Reception-Amplification . . . . 19

Demodulation . . . . 19

Direction Discrimination . . . . 20

High-Pass and Low-Pass Filters . . . . 20

Doppler Spectral Analysis . . . . 20

Fourier Transform Spectral Analysis . . . 21

Limitations of FFT Spectral Analysis . . 22

Analog Fourier Spectral Analysis . . . . . 23

Autoregression Analysis . . . . 23

Continuous-Wave Doppler Ultra- sonography . . . . 24

Pulsed-Wave Doppler Ultrasonography . . 25

Doppler Sample Volume . . . . 25

Artifacts of Spectral Doppler Sonography 26 Nyquist Limit . . . . 26

Implications of Aliasing . . . . 27

Range-Velocity Resolution . . . . 27

Mirror Imaging . . . . 28

Duplex System . . . . 28

Principles of the Duplex Doppler System . . . . 28

Optimal Configuration of a Duplex System: Imaging Versus Doppler System . . . . 29

Duplex Implementation . . . . 30

Electronic Array Scanner . . . . 30

Integration of the Doppler and Imaging Functions in Array Transducer . . . . 31

Multiple-Gate and Multiple-Sample Doppler Systems . . . . 32

Doppler Display . . . . 33

Summary . . . . 33

References . . . . 34

4 Spectral Doppler Sonography: Waveform Analysis and Hemodynamic Interpretation . . . . 35

Dev Maulik Spectral Doppler Sonogram . . . . 35

Doppler Frequency Shift Envelopes . . . 36

Hemodynamic Information from Doppler Sonography . . . . 37

Flow Detection . . . . 37

Flow Direction . . . . 37

Flow Velocity Profile . . . . 38

Doppler Flow Quantification . . . . 38

Principle of Doppler Flowmetry . . . . . 39

Doppler Velocity Measurement . . . . 40

Contents

Determination of Vascular Luminal Area 40 Determination of the Angle

of Insonation . . . . 40

Alternative Methods of Doppler Flowmetry . . . . 41

Non-Doppler Flowmetry ± Time Domain Processing Velocity Measurement . . . . 41

Doppler Waveform Analysis and Doppler Indices . . . . 43

Comprehensive Waveform Analysis . . . 44

Choice of Indices . . . . 45

Sources of Variance of the Doppler Indices . . . . 46

Hemodynamic Basis of Doppler Waveform Analysis . . . . 46

Experimental Approaches to Hemo- dynamic Validation of Doppler Indices . 47 Arterial Input Impedance: Basic Concepts and Relevance to Doppler Waveform Analysis . . . . 47

Doppler Indices and Peripheral Resistance . . . . 49

Doppler Indices and Input Impedance . 49 Doppler Indices and Central Circulation 52 Placental Vascular Changes and Abnormal Doppler Waveforms . . . . 54

Summary . . . . 54

References . . . . 55

5 Venous Haemodynamics . . . . 57

Torvid Kiserud Velocity Profile in Veins . . . . 57

Parabolic Blood Velocity Profile and Flow Calculation . . . . 57

Factors Modifying the Velocity Profile . 58 Pulsation in Veins . . . . 59

Cardiac Function and Waveform . . . . . 59

Transmission Lines . . . . 59

Wave Reflections . . . . 60

Compliance and Reservoir Function of the Umbilical Vein . . . . 61

Direction of Pulse and Blood Velocity . . 63

Source of Pulse . . . . 64

References . . . . 65

6 Sonographic Color Flow Mapping: Basic Principles . . . . 69

Dev Maulik Principles of Doppler Color Flow Mapping 69 Multigated Doppler Interrogation . . . . 69

Color Doppler Signal Analysis . . . . 70

Instrumentation . . . . 71

Color Flow Processor . . . . 71

Transducers for Doppler Color Flow Mapping . . . . 72

Color Mapping . . . . 72

Color Classification . . . . 72

Color Perception . . . . 73

Color Encoding of Doppler Flow Signals 73 Color Mapping of Direction of Flow . . . 73

Color Mapping of Velocity and the Color Bar . . . . 73

Color Mapping of Variance . . . . 74

Formation of a Color Frame . . . . 74

Two-Dimensional Color Frame Formation . . . . 74

Persistence . . . . 75

Frame Rate . . . . 75

M-Mode Color Frame Formation . . . . . 75

Operational Considerations . . . . 76

Transducer Frequency . . . . 76

Pulse Repetition Frequency . . . . 76

Doppler Color Flow Gain . . . . 77

High-Pass Filter (Wall Filter) . . . . 77

Limitations of Doppler Color Flow Mapping . . . . 78

Aliasing . . . . 78

Range Ambiguity . . . . 80

Temporal Ambiguity . . . . 80

Angle of Insonation . . . . 80

Wall Motion Ghost Signals . . . . 81

Mirroring . . . . 81

Color Mapping of Doppler Amplitude (Doppler Power or Doppler Energy) . . . 81

Summary . . . . 83

References . . . . 84

7 Three-dimensional Color and Power Doppler Ultrasonography of the Fetal Cardiovascular System . . . . 85

Rabih Chaoui, Karim D. Kalache Introduction . . . . 85

Technical Background . . . . 85

Equipment . . . . 85

Advantages of Power Doppler for 3D Rendering . . . . 85

Principle of Data Acquisition, Image Rendering, and Display . . . . 85

Limitations of 3D Power Doppler in Prenatal Ultrasound . . . . 87

Clinical Application . . . . 87

Umbilical Cord and Placenta . . . . 87

Intraabdominal Vessels . . . . 87

Renal Vessels . . . . 89

Intracranial Vessels . . . . 90

Lung Vessels . . . . 91

Fetal Tumors or Aberrant Vessels . . . . . 91

XII Contents

Heart and Great Vessels . . . . 92

References . . . . 93

8 Biological Safety of Diagnostic Sonography . . . . 95

Dev Maulik Introduction . . . . 95

Acoustic Output of Diagnostic Ultrasound Devices and Its Regulation . . . . 96

Mechanisms of Bioeffects . . . . 96

Thermal Effects . . . . 96

Acoustic Characteristics . . . . 97

Tissue Characteristics for Thermal Effect 98 Cellular Response to Heating, Acoustic Power, and Temporal Threshold . . . . . 98

Experimental Evidence of Thermal Effects . . . . 98

Acoustic Heating of Fetal Bones . . . . . 99

Acoustic Heating of Fetal Brain . . . . . 99

Clinical Significance of the Ultrasound Thermal Effects . . . . 99

Mechanical Effects . . . . 101

Cavitation . . . . 101

Acoustic Characteristics for Cavitation . 102 Ambient Pressure and Temperature . . 102

Tissue Characteristics for Cavitation . . 102

Biological Effects of Inertial Cavitation . 102 Clinical Significance of Acoustic Cavitation . . . . 103

Experimentally Induced Developmental Bioeffects . . . . 104

Epidemiological Evidence of Developmental Bioeffects . . . . 104

General Outcome . . . . 105

Fetal Movement . . . . 105

Birth Weight . . . . 105

Pediatric Malignancy . . . . 106

Neurodevelopment ± General . . . . 106

Neurodevelopment ± Sinistrality . . . . . 106

Clinical Significance . . . . 107

Guidelines for Clinical Application . . . . 107

References . . . . 108

9 Fetal and Maternal Cardiovascular Physiology . . . . 113

Joseph Itskovitz-Eldor, Israel Thaler Uterine Circulation . . . . 113

Functional Anatomy of the Uteroplacental Circulation . . . . 113

Alterations in Uterine Blood Flow . . . . 114

Regulation of Uteroplacental Circulation 115 Fetal Circulation . . . . 116

Fetal Cardiac Output and Distribution . 117 Regulation of Cardiac Function . . . . 117

Patterns of Venous Returns . . . . 121

Umbilical-Placental Circulation . . . . 123

Cardiovascular Responses to Stress . . . 125

References . . . . 127

10 Umbilical Doppler Velocimetry: Normative Data and Diagnostic Efficacy 133 Dev Maulik Doppler Interrogation of the Umbilical Artery . . . . 133

Continuous-Wave Doppler Interrogation 133 Pulsed-Wave Doppler Interrogation . . . 134

Doppler Display and Archiving . . . . 134

Descriptor Indices of the Umbilical Arterial Doppler Waveform . . . . 134

Reproducibility of Umbilical Arterial Doppler Indices . . . . 135

Continuous-Wave Versus Pulsed-Wave Doppler Indices . . . . 136

Site of Doppler Interrogation . . . . 136

Short-Term Temporal Variations: Diurnal Effect . . . . 137

Long-Term Temporal Variations: Gestational Age Effect . . . . 137

Fetal Heart Rate . . . . 138

Breathing . . . . 140

Behavioral States . . . . 141

Blood Viscosity and Doppler Indices . . . . 141

Maternal Posture and Umbilical Arterial Doppler Indices . . . . 141

Maternal Exercise and Umbilical Arterial Doppler Indices . . . . 142

Summary . . . . 142

References . . . . 142

11 Fetal Descending Aorta . . . . 145

Karel Marsϗl Fetal Aortic Doppler Velocimetry . . . . 146

Aortic Flow Estimation . . . . 146

Aortic Velocity Waveform Analysis . . . 147

Fetal Aortic Flow in Uncomplicated Pregnancies . . . . 149

Intrinsic Influences on Fetal Aortic Flow and Flow Indices . . . . 151

Fetal Aortic Blood Flow During Labor . . . 151

Pathophysiologic Changes of Fetal Aortic Flow During Intrauterine Hypoxia . . . . 151

Clinical Studies . . . . 153

Fetal Cardiac Arrhythmias . . . . 153

Fetal Anemia . . . . 153

Diabetes Mellitus . . . . 154

Intrauterine Growth Restriction . . . . 154

a Contents XIII

Aortic Doppler Velocimetry as a Diagnostic

Test of IUGR and Fetal Hypoxia . . . 154

Follow-up Studies . . . 155

Summary . . . 156

References . . . 156

12 Intrauterine Blood Flow and Postnatal Development . . . 161

David Ley, Karel Marsϗl Background . . . 161

Neurodevelopmental Outcome in IUGR 161 IUGR and Cardiovascular Morbidity . . . 162

Postnatal Implications of Abnormal Fetal Blood Flow . . . 162

Neonatal Outcome . . . 162

Long-Term Neurodevelopmental Implications . . . 163

The Malmæ±Lund Study . . . 167

Background Material . . . 167

Fetal Aortic Blood Flow and Postnatal Neurodevelopment . . . 167

Fetal Aortic Blood Flow and Postnatal Cardiovascular Function . . . 170

Conclusion . . . 171

References . . . 172

13 Cerebral and Umbilical Doppler in the Prediction of Fetal Outcome . . . . 177

Philippe Arbeille, Gabriel Carles, Murielle Chevillot, Alain Locatelli, Philippe Herve, Frank Perrotin, Dev Maulik Fetal Cerebral Flow Adaptation to Hypoxia 177 Examination Technique . . . 177

Human Investigations (Duplex B, Pulsed Wave Doppler, and Color Doppler) . . . 177

Animal Investigations (Implanted Doppler Sensors) . . . 179

Cerebral Hemodynamics and Doppler Indices . . . 179

Cerebral Resistance to Flow . . . 179

Cerebral±Umbilical Ratio for Evaluating pO

Changes . . . 180

Effect of Fetal Heart Rate on Doppler Vascular Resistance Indices . . . 180

Hypoxic Index for Predicting Effect of Hypoxia . . . 183

Cerebral Circulation in Normal Pregnancy . 184 Cerebral Flow Changes with Gestational Age . . . 184

Variations According to the Site of Examination . . . 185

Cerebral Flow Changes with Behavioral States . . . 185

Clinical Significance of Cerebral and Cerebral/Umbilical Indices . . . 185

Cerebral Flow in Growth-restricted and Hypoxic Human Fetuses . . . 185

Cerebral±Umbilical Ratio Change in Case of Hypoxia and IUGR . . . 186

Cerebral±Umbilical Ratio and Perinatal Outcome . . . 186

Hypoxic Index for Predicting Effect Hypoxia . . . 186

Cerebro-Vascular Reactivity Tests (O

, CO

) . . . 187

Cerebral Resistance Index, Flow Redistribu- tion Ratio (C/U), and Hypoxic Index in Specific Human Pathologies . . . 187

Cerebral Resistance Index and C/U Ratio in Acute Reversible Hypoxia: Prediction of Abnormal FHR at Delivery . . . 187

C/U Ratio in Non-Reversible Hypoxia (Pregnancy-Induced Hypertension) Prediction of Abnormal FHR at Delivery 188 Cerebral Flow During Maternal Anesthesia . . . 190

Cerebral Flow Response to Induced Hypoxia and Drugs in Animal Models . . . 190

Cerebral Flow and Long-Term Nicotine Treatment (Animal Model) . . . 190

Cerebral Flow and Long-Term Cocaine Treatment (Animal Model) . . . 191

Cerebral±Umbilical Ratio and Mechanically Induced Hypoxia . . . 192

Cerebral±Umbilical Ratio and Acute Drug Effect . . . 192

Conclusion . . . 192

References . . . 195

14 Cerebral Blood Flow Velocity Waveforms: Clinical Application . . . 199

Laura Detti, Maria Segata, Giancarlo Mari Which Is the Cerebral Vessel to Assess in the Fetus? . . . 199

Cerebral Blood Flow Velocity Waveforms in the IUGR Fetus . . . 200

Cerebral±Placental Ratio . . . 202

What to Do in Presence of an Abnormal Cerebral±Placental Ratio? . . . 202

Prediction of Fetal Hematocrit . . . 202

Red Cell Alloimmunization and MCA Peak Systolic Velocity . . . 203

MCA-PSVin Other Causes of Fetal Anemia . . . 206

References . . . 207

XIV Contents

15 Pulsed Doppler Ultrasonography

of the Human Fetal Renal Artery . . . . . 211 Jean-Claude Veille

Doppler Principles and Hints . . . . 212 Clinical Application: Fetal Renal Artery

Doppler Assessment . . . . 213 Fetal Renal Doppler Imaging . . . . 213 Renal Artery Doppler Studies in the

Normal Fetus . . . . 213 Renal Artery Doppler Studies in IUGR

Fetuses . . . . 216 Fetal Renal Artery Doppler Studies

and Postterm Pregnancy . . . . 218 Fetal Renal Artery Doppler Studies

and Intravascular Transfusion . . . . 219 Fetal Renal Artery Doppler Studies

and Maternal Drug Intake . . . . 219 Fetal Renal Artery and Fetal Anomalies 220 Quantitation of Fetal Renal Blood Flow 221 References . . . . 223

16 Doppler Velocimetry

of the Uteroplacental Circulation . . . . . 227 Edwin R. Guzman, Eftichia Kontopoulos,

Ivica Zalud

Introduction . . . . 227 Non-Doppler Methods to Measure Uterine Artery Blood Flow . . . . 227 Anatomy of Uterine Circulation . . . . 227 Normal Growth and Development

of Uteroplacental Circulation During

Pregnancy . . . . 228 Abnormal Development of the Utero-

placental Circulation in the Presence of Essential Hypertension, Preeclampsia,

and Intrauterine Growth Restriction . . . . 229 Indices of Uterine Artery Waveform

Analysis . . . . 231 Normal and Abnormal Development of

Uterine Artery Doppler Waveform . . . . 231 Uterine Artery Diameter and Volume

Flow . . . . 233 Uterine Artery Maximum and Mean

Flow Velocity . . . . 235 Uterine Artery Waveform Notch . . . . 235 Influence of Placental Location

on Uterine Artery Waveforms . . . . 238 Doppler Waveforms of the Arcuate, Radial, and Spiral Arteries . . . . 240 Effect of Pharmacologic Agents and

Epidural Anesthesia on Uterine Artery

Waveforms . . . . 241 Effects of Exercise on Uterine Velocimetry 242

Effects of Uterine Contractions on Uterine Waveforms . . . . 242 Uterine Artery Circulation with Uterine

Anomalies . . . . 242 Uterine Velocimetry and Umbilical Vein

Gases . . . . 243 Uterine Artery Screening During

Pregnancy . . . . 243 Biochemical Serum Markers and Uterine

Artery Doppler Velocimetry . . . . 245 Medical Attempts at Modification

of Pregnancy Outcome in Women with Abnormal Uterine Artery Doppler

Velocimetry . . . . 245 Medical Conditions and Uterine Artery

Doppler Velocimetry . . . . 248 Uterine Artery Doppler Velocimetry in

IUGR Fetuses and Hypertensive Disorders of Pregnancy . . . . 248 Conclusions . . . . 250 References . . . . 251

17 Doppler Velocimetry

of the Uteroplacental Circulation

During Early Pregnancy . . . . 255 Israel Thaler, Amnon Amit

Maternal Vascular Response

to Placentation . . . . 255 Regulation of Uteroplacental Blood Flow . 258 Prostacyclins . . . . 259 Endothelium-Derived Relaxing Factor . 260 Endothelin . . . . 262 Doppler Velocimetry of the Uteroplacental Circulation . . . . 262

Methodology . . . . 262 Anatomic Considerations . . . . 264 Changes in Uteroplacental Blood Flow

During Early Normal Pregnancy . . . . 266 Doppler Velocimetry During Early

Pregnancy and Pregnancy Outcome . . . . 269 Normal Early Pregnancy and Early

Pregnancy Failure . . . . 269 Screening for Preeclampsia and

Intrauterine Growth Restriction . . . . 270 References . . . . 275

a Contents XV

18 Doppler Ultrasound in the Diagnosis and Management

of Intrauterine Growth Restriction . . . . 281

William J. Ott Introduction . . . 281

The Antenatal Diagnosis of IUGR . . . 282

Doppler Ultrasound . . . 283

Uterine Arteries . . . 285

Other Ultrasonic Methods of Diagnosing IUGR . . . 286

Evaluation and Follow-up of Suspected IUGR . . . 286

Umbilical Artery Doppler . . . 286

Central Nervous System Blood Flow . . . 287

Venous Doppler . . . 289

Conclusion . . . 291

References . . . 293

19 Doppler Velocimetry and Hypertension 299 Hein Odendaal Introduction . . . 299

Uterine Artery . . . 299

Screening in the First Trimester . . . 299

Screening in the Second Trimester . . . . 299

Screening in the Third Trimester . . . 301

Method of Screening (Quantifying Poor Diastolic Flow Velocity) . . . 301

The Effect of Gestational Age . . . 301

Position of the Placenta . . . 301

Overview . . . 301

Time to Establish the Ground Values . . 302

Other Predictions . . . 302

Aspirin . . . 302

Summary . . . 302

Umbilical Artery Doppler . . . 303

Clinical Findings . . . 303

Umbilical Artery Flow Velocity Wave- forms in Low-Risk Populations . . . 304

Umbilical Artery Flow Velocity Wave- forms in High-Risk Pregnancy . . . 304

Doppler Ultrasound and HELLP Syndrome . . . 304

Effect of Antenatal Steroids . . . 304

Fetal Assessment Before Admission to Hospital . . . 304

Fetal Assessment in Hospital . . . 305

When Should the Patient Be Delivered for Severe Pre-eclampsia? . . . 305

Abruptio Placentae . . . 305

Congenital Abnormalities . . . 306

Severe Asphyxia . . . 306

In Utero Treatment in Cases of Poor Umbilical Artery Doppler Velocimetry . 306 When to Deliver for Reverse End- Diastolic Velocity . . . 306

When to Deliver for Absent End- Diastolic Velocity . . . 306

Method of Delivery . . . 307

Other Effects on Umbilical Artery Doppler Flow Velocity Waveforms . . . . 307

Neonatal Outcome . . . 307

Conclusion . . . 307

References . . . 307

20 Doppler Velocimetry and Multiple Gestation . . . 313

Emanuel P. Gaziano, Ursula F. Harkness Twin Prevalence . . . 313

Twin Placentation . . . 313

Fetal Doppler and Complications of Multiple Gestation . . . 315

Growth Restriction and Discordance . . 315

Twin Transfusion Syndrome . . . 319

Doppler Velocimetry and Outcome in Twin Pregnancies . . . 324

Future Research . . . 327

Conclusion . . . 327

References . . . 327

21 Doppler Sonography in Pregnancies Complicated with Pregestational Diabetes Mellitus . . 331

Dev Maulik, Genevieve Sicuranza, Andrzej Lysikiewicz, Reinaldo Figueroa Introduction . . . 331

Maternal Glycemic State and Fetal Hemodynamics . . . 331

Umbilical Artery Doppler Sonography in Diabetic Pregnancies . . . 332

Umbilical Artery Doppler and Perinatal Outcome . . . 332

Umbilical Arterial Doppler Sonography and Maternal Glycemic Control . . . 333

Doppler Sonography of Other Fetal and the Uterine Circulations in Pregestational Diabetic Pregnancies . . . 333

Fetal Middle Cerebral Artery Doppler . . 333

Fetal Cardiac Doppler . . . 334

Uterine Artery Doppler . . . 334

Clinical Effectiveness and Guidelines . . . . 335

Conclusion . . . 336

References . . . 336

XVI Contents

22 Doppler Velocimetry

in Maternal Alloimmunization . . . . 339

Andrzej Lysikiewicz Doppler Velocimetry as the Preferred Diagnostic Tool . . . . 339

Maternal Alloimmunization and Fetal Disease . . . . 339

Fetal Pathophysiology in Alloimmunization 339 Fetal Anemia . . . . 339

Fetal Cardiovascular Changes in Alloimmunization . . . . 340

Cardiac Blood Flow . . . . 340

Fetal Heart Rate . . . . 340

Sinusoidal Fetal Heart Rate . . . . 340

Changes in Fetal Systemic Arterial Blood Flow . . . . 341

Doppler Flow Velocity Measurements . 341 Fetal Aortic Arch . . . . 341

Fetal Descending Aorta . . . . 341

Splenic Artery . . . . 342

Renal Arteries . . . . 342

Umbilical Arteries . . . . 342

Internal Carotid Artery . . . . 342

Middle Cerebral Artery . . . . 342

Changes in Fetal Venous Blood Flow . . . . 344

Umbilical Vein . . . . 344

Inferior Vena Cava Blood Flow . . . . 344

Ductus Venosus . . . . 345

Maternal Uterine Artery . . . . 345

Fetal Morphologic Changes and Doppler Velocimetry in Alloimmunization . . . . 345

Fetal Blood Redistribution and Fetal Hypoxia in Alloimmunization . . . . 346

Doppler Velocimetry in Clinical Management of Alloimmunization . . . 346

History of Previous Pregnancy . . . . 346

Maternal Antibody Titer . . . . 346

Amniotic Fluid Densitometry . . . . 346

Detecting Fetal Anemia . . . . 346

Diagnostic Invasive Procedures to Detect Fetal Anemia and Doppler Velocimetry 348 Doppler Monitoring During Cordocentesis 348 Fetal Intravascular Transfusions . . . . 348

Early Delivery . . . . 349

Noninvasive Therapies, Gamma Globulin, Plasmapheresis, Nonintervention . . . . 349

Conclusion . . . . 349

References . . . . 350

23 Doppler Velocimetry in Prolonged Pregnancy . . . . 353

Ray O. Bahado-Singh, Maria Segata, Chin-Chien Cheng, Giancarlo Mari Introduction . . . . 353

Umbilical Artery Doppler . . . . 353

Umbilical Artery Doppler Versus Other Antepartum Tests . . . . 356

Middle Cerebral Artery Doppler Veloci- metry . . . . 357

Aortic Blood Flow Doppler . . . . 358

Aorta and Pulmonary Artery Doppler . . . 359

Renal Artery Doppler . . . . 359

Uterine and Uteroplacental Artery Doppler 360 Conclusion . . . . 361

References . . . . 361

24 Doppler Velocimetry for Fetal Surveillance: Adverse Perinatal Outcome and Fetal Hypoxia . . . . 363

Dev Maulik, Reinaldo Figueroa Doppler Velocimetry and Adverse Perinatal Outcome . . . . 364

Diagnostic Efficacy of Doppler Veloci- metry Among High-Risk Pregnancies . 365 Fetal Doppler Velocimetry, Nonstress Test, and Biophysical Profile: Compara- tive Efficacy for Predicting Adverse Peri- natal Outcome . . . . 366

Fetal Doppler Sonography and Neuro- developmental Outcome . . . . 367

Efficacy of Doppler Sonography for Screening Low-Risk and Unselected Pregnancies . . . . 367

Doppler Velocimetry and Fetal Hypoxia- Asphyxia . . . . 368

Fetal Asphyxia and Umbilical and Aortic Doppler Indices . . . . 368

Efficacy of Doppler Method . . . . 368

Comparative Efficacy of Doppler Veloci- metry and Other Methods of Fetal Sur- veillance . . . . 369

Fetal Asphyxia and Cerebral Doppler Sonography . . . . 370

Sequence of Changes in Fetal Surveillance Parameters with Progressive Antepartum Fetal Compromise . . . . 371

Summary . . . . 372

References . . . . 373

a Contents XVII

25 Absent End-Diastolic Velocity in the Umbilical Artery

and Its Clinical Significance . . . 375

Dev Maulik, Reinaldo Figueroa Incidence . . . 376

Technical Considerations . . . 376

Absent End-Diastolic Velocity and Adverse Perinatal Outcome . . . 377

Perinatal Mortality . . . 377

Perinatal Morbidity . . . 377

Maternal Hypertension and Absent End- Diastolic Velocity . . . 382

Reappearance of End-Diastolic Velocity . . 382

AREDVand Other Emergent Signs of Fetal Compromise . . . 383

Summary . . . 384

References . . . 384

26 Doppler Velocimetry for Fetal Surveil- lance: Randomized Clinical Trials and Implications for Practice . . . 387

Dev Maulik, Reinaldo Figueroa Doppler Randomized Trials: A Summary . . 387

Doppler Randomized Trials: Cumulative Summary . . . 392

Population Characteristics . . . 392

Objective and Primary Outcome . . . 393

Doppler Sonographic Technique and Research Design . . . 393

Management Protocol . . . 393

Doppler Randomized Trials: Meta-Analysis 393 Meta-Analysis: Brief Introduction . . . 393

Doppler Meta-Analysis . . . 395

Management of High-Risk Pregnancy: A Proposal Based on Clinical Trials . . . 398

Conclusion . . . 399

References . . . 399

27 Doppler Investigation of the Fetal Inferior Vena Cava . . . 403

Yoshihide Chiba, Toru Kanzaki, Zeev Weiner Normal Blood Flow Pattern in Fetal IVC . . 403

Doppler Evaluation of Preload Condition in the Fetal Vena Cava and the Umbilical Vein . . . 404

Preload Index . . . 404

Blood Flow Change During Fetal Therapy . . . 406

Blood Flow Dynamics in Fetal Central Veins During Labor . . . 406

IVC Blood Flow at an Early Stage of Pregnancy . . . 407

Abnormal IVC Blood Flow Patterns with Fetal Arrhythmias . . . 407

Blood Flow Pattern of Premature Contractions . . . 408

Bradycardic Arrhythmia . . . 408

Tachyarrhythmias . . . 408

Determination of Fetal Therapy According to the Type of Tachycardia . 410 IVC and Umbilical Vein Blood Flow Patterns in High-Risk Fetuses . . . 410

References . . . 411

28 Ductus Venosus . . . 413

Torvid Kiserud Anatomy and Development . . . 413

Physiological Background . . . 414

Via Sinistra . . . 414

Umbilical Liver Perfusion . . . 415

Portal Watershed Area . . . 416

Porto-Caval Pressure Gradient . . . 416

Fetal Respiratory Force . . . 416

Postnatal Physiology . . . 416

Ultrasound Imaging and Insonation . . . 417

Normal Ductus Venosus Blood Velocity . . 418

Waveform Analysis: Indices . . . 419

Interpretation of the Waveform . . . 420

The Atrial Contraction Wave . . . 420

Systolic Wave . . . 421

Pitfalls . . . 421

Reproducibility . . . 422

Agenesis of the Ductus Venosus . . . 423

References . . . 423

29 Doppler Ultrasound Examination of the Fetal Coronary Circulation . . . 429

Ahmet Alexander Baschat Introduction . . . 429

Embryology and Functional Anatomy of the Coronary Circulation . . . 429

Ultrasound Examination Technique . . . 430

Ultrasound Setup . . . 430

Examination of Coronary Arteries . . . . 431

Examination of the Coronary Sinus . . . 432

Clinical Applications in Fetuses with Normal Cardiac Anatomy . . . 436

The ªHeart-Sparing Effectº in Fetal Growth Restriction . . . 436

Fetal Anemia . . . 436

Ductus Arteriosus Constriction . . . 437

Other Fetal Conditions . . . 437

XVIII Contents

Clinical Applications in Fetal Cardiac

Abnormalities . . . . 437

Ventriculocoronary Connections in the Human Fetus . . . . 437

Coronary Arteriovenous Fistula in the Human Fetus . . . . 438

Idiopathic Arterial Calcification in the Human Fetus . . . . 438

Critical Aortic Stenosis . . . . 439

Persistent Left Superior Vena Cava . . . 439

References . . . . 439

30 Doppler Interrogation of the Umbilical Venous Flow . . . . 443

Enrico Ferrazzi, Serena Rigano Introduction . . . . 443

Fetal Flow Volume Measurements in the Era of Digital Computing and Imaging . . 443

Sources of Inaccuracies . . . . 443

Source of Accuracy . . . . 444

Volume Flow Values and Problems of Standardization . . . . 444

Comparison Between Non-Invasive Doppler Volume Flow Values and Traditional Experimental Studies . . . . . 445

From Umbilical Flow Volume Measure- ments to Fetal Pathophysiology . . . . 445

The Relationship of Umbilical Vein Blood Flow to Growth Parameters in the Human Fetus . . . . 445

Umbilical Vein Blood Flow and Abnor- mal Fetal Growth . . . . 445

Diagnostic Usage of Umbilical Vein Blood Flow in Growth-Restricted Fetuses . . . . 446

Redistribution of Umbilical Flow in Fetal Liver . . . . 447

References . . . . 448

31 Doppler Examination of the Fetal Pulmonary Venous Circulation . . . . 451

Rabih Chaoui, Franka Lenz, Kai-Sven Heling Introduction . . . . 451

Visualization of Pulmonary Veins Using Real-Time and Color Doppler Ultrasound . 451 Pulsed Doppler Ultrasound of Lung Veins 453 Physiologic Conditions . . . . 453

Abnormal Patterns of Flow Velocity Waveforms . . . . 455

Other Fields of Interest Assessing Pulmonary Vein Doppler . . . . 456

Malformations of Pulmonary Veins and Their Diagnosis . . . . 457

Embryology in Summary . . . . 457

Anomalies of the Pulmonary Venous Connections . . . . 458

Prenatal Diagnosis of Anomalous Pulmonary Venous Connection . . . . 458

References . . . . 462

32 Introduction to Fetal Doppler Echocardiography . . . . 465

Dev Maulik Introduction . . . . 465

Choice of Equipment for Doppler Echocardiography . . . . 465

General Considerations . . . . 465

Ultrasound System . . . . 466

Preparation for Echocardiographic Examination . . . . 466

Method of Fetal Doppler Echo- cardiography . . . . 467

Preliminary Examination . . . . 467

General Approach to Fetal Cardiac Imag- ing . . . . 467

Spectral Doppler Sonographic Examina- tion . . . . 471

Color Doppler Flow Mapping . . . . 472

Spectral and Color Doppler M-Mode Echocardiography . . . . 473

Tissue Doppler Echocardiography . . . . 474

Doppler Depiction of Fetal Cardiac Circulation . . . . 475

Atrial Flow . . . . 476

Interatrial Flow . . . . 477

Tricuspid and Mitral Flow . . . . 477

Pulmonary and Aortic Outflows . . . . . 479

Doppler Echocardiography During Early Pregnancy . . . . 480

Determination of Fetal Cardiac Output . . 480

Cardiac Output: Normative Data . . . . . 481

Right Heart Versus Left Heart Dominance . . . . 482

Limitations of Cardiac Output Measurement . . . . 482

Summary . . . . 482

References . . . . 482

33 Doppler Echocardiography for Managing Congenital Cardiac Disease . . . . 485

Dev Maulik Introduction . . . . 485

Risk Factors and Indications for Fetal Cardiac Evaluation . . . . 485

Benefits of Fetal Echocardiographic Assessment . . . . 486

a Contents XIX

Utility of Fetal Doppler Echocardiographic

Assessment . . . 487

In Utero Evolution of Cardiac Malformations . . . 487

Doppler Characterization of Congenital Cardiac Malformations . . . 488

Doppler Echocardiographic Assessment of Specific Cardiac Anomalies . . . 491

Cardiac Position . . . 491

Atrial, Atrioventricular, and Ventricular Anomalies . . . 493

Outflow Tract Anomalies . . . 497

Fetal Cardiac Arrhythmias . . . 499

General Principles . . . 499

Premature Atrial Contractions . . . 500

Supraventricular Tachycardia . . . 501

Congenital Complete Heart Block . . . . 503

Summary . . . 505

References . . . 505

34 Four-Dimensional B-Mode and Color Doppler Echocardiography of the Human Fetus . . . 509

Dev Maulik Introduction . . . 509

History of Four-Dimensional Echo- cardiography . . . 509

Basic Principles of Three- and Four- Dimensional B-Mode and Doppler Sonography . . . 510

Two-Dimensional Matrix Array . . . 510

Two-Dimensional Matrix Array: Fetal Application of the Technique . . . 512

Motorized Curved Linear-Array System and Spatio-Temporal Image Correlation . . 513

Fetal Echocardiography with STIC Technology . . . 514

Conclusion . . . 515

References . . . 516

35 Doppler Echocardiographic Assessment of Fetal Cardiac Failure . . . 517

William J. Ott Introduction . . . 517

Fetal Cardiac Anatomy and Physiology . . . 517

Fetal Cardiac Response to Stress . . . 519

The Scope of Fetal Cardiac Failure . . . 520

Duplex Doppler Evaluation of the Fetal Cardiovascular System . . . 520

Umbilical Venous Pulsations . . . 521

Other Studies . . . 521

Velocity Measurements Across the Atrioventricular Valves . . . 522

Ventricular Outflow Velocities . . . 523

Ductus Arteriosus . . . 523

Errors in Doppler Blood Flow Velocity Measurements . . . 523

Clinical Conditions Associated with Fetal Heart Failure . . . 524

Congenital Heart Disease . . . 524

Fetal Hydrops . . . 526

Twin±Twin Transfusion Syndrome . . . . 530

Intrauterine Growth Restriction . . . 531

Diabetes Mellitus . . . 531

Other Causes of Fetal Heart Failure . . . 532

Summary and Conclusion . . . 532

References . . . 533

36 Doppler Echocardiographic Studies of Deteriorating Growth-Restricted Fetuses . . . 537

Domenico Arduini, Giuseppe Rizzo Pathophysiology . . . 537

General Principles of Doppler Echo- cardiography for Functional Study of Fetal Cardiac Function . . . 538

Fetal Circulation . . . 538

Doppler Echocardiographic Technique . 538 Parameters Measured . . . 538

Recording Sites and Velocity Waveforms: Characteristics and Significance . . . 538

Longitudinal Hemodynamic Modifications in IUGR Fetuses . . . 539

Umbilical Artery . . . 540

Fetal Peripheral Vessels . . . 540

Cerebral Vessels . . . 540

Fetal Cardiac Flows . . . 541

Fetal Venous Flows . . . 542

Conclusions . . . 543

References . . . 544

37 Evaluation of Pulmonary and Ductal Vasculature: Fetal Echocardiography for Evaluation of Therapy for Preterm Labor . . . 547

James C. Huhta, Gerald Tulzer, Sharon R. Weil-Chalker Fetal Examination Technique . . . 547

Fetal Echocardiography . . . 547

Peripheral Doppler/Cardiac Doppler Sonography . . . 548

Fetal Ductal Evaluation . . . 550

Normal Doppler Waveforms . . . 551

Ductal Constriction After Therapy for Preterm Labor . . . 551

Ductal Occlusion . . . 553

XX Contents

Terbutaline . . . . 554

Terbutaline Effect Versus Ductal Constriction . . . . 555

Fetal Pulmonary Assessment . . . . 555

Summary . . . . 555

References . . . . 556

38 Three-Dimensional Doppler Ultrasound in Gynecology . . . . 557

Ivica Zalud, Lawrence D. Platt Technique . . . . 557

3D Doppler Measurements . . . . 558

3D Doppler in Human Reproduction . . . . 558

3D Doppler in Gynecologic Oncology . . . 562

3D Doppler in Benign Gynecology . . . . . 564

Conclusion . . . . 567

References . . . . 567

39 Doppler Ultrasonography for Benign Gynecologic Disorders, Ectopic Pregnancy, and Infertility . . . . 569

Ivica Zalud Examination Technique . . . . 569

Normal Pelvic Blood Flow . . . . 570

Benign Uterine Pathology . . . . 572

Fibroids/Leiomyomas . . . . 572

Endometrium . . . . 573

Retained Products of Conception . . . . 574

Benign Adnexal Pathology . . . . 575

Endometriosis . . . . 576

Pelvic Inflammatory Disease . . . . 576

Doppler Ultrasound and Ectopic Pregnancy . . . . 578

Other Types of Ectopic Pregnancy . . . . . 582

Interstitial/Cornual Pregnancy . . . . 582

Management . . . . 584

Conservative Management . . . . 584

Ultrasound Monitoring of Conservative Management . . . . 586

Doppler Ultrasound and Infertility . . . . . 587

Uterine Blood Flow during Menstrual Cycle . . . . 587

Ovarian Blood Flow during Menstrual Cycle . . . . 589

Clinical Application . . . . 590

Conclusion . . . . 592

References . . . . 594

40 Doppler Ultrasonography for Gynecologic Malignancies . . . . 599

Ivica Zalud Angiogenesis in Tumors of Low Malignant Potential . . . . 600

Angiogenesis in Malignant Ovarian Masses . . . . 600

Ovarian Cancer . . . . 602

Malignant Uterine Conditions . . . . 603

Potential of Screening . . . . 603

Three-Dimensional Ultrasound . . . . 604

Pitfalls and Artifacts . . . . 606

Conclusions . . . . 608

References . . . . 608

a Contents XXI

Amon Amit, MD

Department of Pathology, Rambam Medical Center, Haifa 31096, Israel

Philippe Arbeille, MD, PhD Unit INSERM 316, CHU Trousseau, 37044 Tours, France

Domenico Arduini, MD

Department of Obstetrics and Gynecology,

University di Roma ªTor Vergataº, Ospedale Fatebenefratelli, Isola Tiberina 39, 00186 Rome, Italy

Ray O. Bahado-Singh, MD

Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA Ahmet Alexander Baschat, MD

Center for Advanced Fetal Care, Department of Obstetrics,

Gynecology and Reproductive Sciences, University of Maryland, Baltimore,

22 South Greene Street, Baltimore, MD 21201, USA Gabriel Carles, MD

Department of Obstetrics and Gynecology, Hopital de Saint Laurent du Maroni 97320, France Rabih Chaoui, MD, Prof.

Department of Obstetrics and Gynecology, Charit Medical School, Humboldt University, Schumannstrasse 20/21, 10098 Berlin, Germany Chin-Chien Cheng, MD

Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA Murielle Chevillot, MD

Dpartment Obstetrique et Gynecologie, CHU Bretonneau, 37044 Tours, France Yoshihide Chiba, MD, PhD

National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan

Laura Detti, MD

Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, 234 Albert Sabin Way, Cincinnati, OH 45267, USA

Enrico M. Ferrazzi, MD

Professor and Chairman, Department of Obstetrics and Gynecology, Institute for Clinical Sciences Sacco, University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy Reinaldo Figueroa, MD

Department of Obstetrics and Gynecology, Winthrop University Hospital, 259 First Street, Mineola, NY 11501, USA

Emanuel P. Gaziano, MD

Abbott Northwestern Hospital, 800 East 28th Street, Minneapolis, MN 55407, USA

Edwin R. Guzman, MD

Department of Obstetrics and Gynecology, MOB 4th Floor, St. Peter's University Hospital, 254 Easton Avenue, New Brunswick, NJ 08903-0591, USA

Ursula F. Harkness, MD, MPH Department of Obstetrics, Gynecology and Women's Health

University of Minnesota 420 Delaware Street SE

Minneapolis, Minnesota, 55455, USA Kai-Sven Heling

Department of Obstetrics and Gynecology, Charit Medical School, Humboldt University, Schumannstrasse 20/21, 10098 Berlin, Germany Philippe Herve, MD

Unit INSERM 316, CHU Trousseau, 37044 Tours, France James C. Huhta, MD

All Children's Hospital, 880 Sixth Street South, Suite 280, St. Petersburg, FL 33701, USA

Joseph Itskovitz-Eldor, MD, DSc

Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa 31096, Israel Karim D. Kalache, MD

Department of Obstetrics and Gynecology, Charit Medical School, Humboldt University, Schumannstrasse 20/21, 10098 Berlin, Germany Toru Kanzaki, MD

Department of Obstetrics and Gynecology, Faculty of Medicine, Rambam Medical Center, Technion, Israel Institute of Technology, Haifa 31096, Israel

Authors

Torvid Kiserud, MD, PhD

Institute of Clinical Medicine, Department of Obstetrics and Gynecology, University of Bergen, 5021 Bergen, Norway Eftichia Kontopoulos, MD

Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, USA Franka Lenz, MD

Department of Obstetrics and Gynecology, Charit Medical School, Humboldt University, Schumannstrasse 20/21, 10098 Berlin, Germany David Ley, MD

Department of Obstetrics and Gynecology, Lund University Hospital, 22185 Lund, Sweden Alain Locatelli, MD

Station INRA-PRMD, Nouzilly, 37380 Monnaie, France Andrzej Lysikiewicz, MD, PhD

Department of Obstetrics and Gynecology,

Winthrop University Hospital, 259 First Street, Mineola, NY 11501, USA

Giancarlo Mari, MD

Department of Obstetrics and Gynecology Hutzel Hospital/Wayne State University 4707 St. Antoine Boulevard

Detroit, Michigan, 48201, USA Karel Marɗl, MD, PhD

Department of Obstetrics and Gynecology, Lund University Hospital, 221 85 Lund, Sweden Dev Maulik, MD, PhD

Department of Obstetrics and Gynecology,

Winthrop University Hospital, Mineola, NY 11501, USA Hein Odendaal, MBChB FCOG(SA), FRCOG, MD Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of Stellenbosch, Stellenbosch, South Africa

William J. Ott, MD, FACOG

Division of Maternal Fetal Medicine, St. John's Mercy Medical Center, Professor, Clinical Obstetrics, Gynecology and Women's Health, St. Louis University Medical School, St. Louis, Missouri, USA

Frank Perrotin, MD

Department of Obstetrics and Gynecology, CHU Bretonneau, 37044 Tours, France Lawrence D. Platt, MD, FACOG

Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Center for Fetal Medicine and Women's Ultrasound, Los Angeles, California 90048, USA

Serena Rigano, MD, PhD

Institute for Clinical Sciences Sacco, University of Milan, Milan, Italy Giuseppe Rizzo, MD

Department of Obstetrics and Gynecology,

University di Roma ªTor Vergataº, Ospedale Fatebenefratelli, Isola Tiberina 39, 00186 Rome, Italy

Maria Segata, MD

Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA Genevieve Sicuranza, MD

Department of Obstetrics and Gynecology,

Winthrop University Hospital, Mineola, NY 11501, USA Israel Thaler, MD

Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa 31096, Israel Gerald Tulzer, MD

Department of Pediatric Cardiology, Children's Hospital of Linz, Herrenstrasse 20, 4020 Linz, Austria Jean-Claude Veille, MD

Department of Obstetrics and Gynecology, Albany Medical Center, MC 74, 43 New Scotland Avenue, Albany, NY 12208, USA

Sharon R. Weil-Chalker, MD

Department of Pediatrics, Abington Memorial Hospital, 1200 Old York Road, Abington, PA 19001, USA Zeev Weiner, MD

Department of Obstetrics and Gynecology, Haemek Medical Center, Afula, Israel

Ivica Zalud, MD, PhD

Fetal Diagnostic Center, Rm 540, Kapiolani Medical Center for Women and Children, 1319 Punahou Street, Honolulu, HI 96826, USA

XXIV Authors